Comparative actions of immunosuppressants, glucocorticoids and non-steroidal anti-inflammatory drugs on various models of delayed hypersensitivity and on a non-immune inflammation in mice.
Various models of delayed hypersensitivity (DH) were used in mice: contact hypersensitivity reactions to picryl chloride and oxazolone and reactions to methylated bovine serum albumin (MBSA) and sheep red blood cells (SRBC). Drugs of different classes were tested in these models by systemic treatment around the challenge period: non-steroidal anti-inflammatory drugs (cyclooxygenase inhibitors, and inhibitors of both cyclooxygenase and lipoxygenase); glucocorticoids and immunosuppressants (cyclosporin A. CsA; cyclophosphamide, Cy; methotrexate, Mtx; azathioprine, Aza). These compounds were also studied and compared for their effects on the 3-h and 24-h phase of the carrageenin mouse-paw edema (in which inflammation is maximal after 24 h). Non-steroidal anti-inflammatory drugs (including double inhibitors of cyclooxygenase and lipoxygenase) had little or no effect on DH models, except indometacin. Glucocorticoids inhibited all immune reactions except that to MBSA. Of the immunosuppressants, CsA reduced all the DH reactions while Aza mainly reduced the reaction to SRBC; Cy and Mtx were mainly active on SBRC and MBSA inflammations. On another hand CsA, Cy and Mtx were inactive on the 3-h phase but decreased the 24-h phase of carrageenin edema. At doses active on the DH models and on carrageenin inflammation, Cy induced a lasting blood leukopenia, but CsA and Mtx did not. This combination of tests in the mouse seems to be of interest to demonstrate any action on DH and any anti-inflammatory effect and to suggest whether these activities are related to a possible leukopenic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Tarayre
J P
JP
Department of Pharmacology A, P. Fabre Research Center, Castres, France.
Barbara
M
M
Aliaga
M
M
Tisne-Versailles
J
J
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002351:Carrageenan; D003877:Dermatitis, Contact / Q000188:drug therapy; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology; D005938:Glucocorticoids / Q000494:pharmacology* / Q000633:toxicity; D006968:Hypersensitivity, Delayed / Q000188:drug therapy*; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000633:toxicity; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007700:Kinetics; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D010081:Oxazolone; D010853:Picryl Chloride; D012710:Serum Albumin, Bovine / Q000276:immunology; D012756:Sheep / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D010081:Oxazolone; D012710:Serum Albumin, Bovine; D002351:Carrageenan; D010853:Picryl Chloride